A dual-functional lanthanide nanoprobe for both living cell imaging and ICP-MS quantification of active protease

Real-time imaging and quantitative monitoring of dynamic changes in biomolecules in bioprocesses is in urgent need for biological and clinical studies. However, this goal is difficult to achieve due to the incompatibility between the commonly used imaging and quantification methods. To fulfill this need, we developed the first nanoprobe capable of both living cell imaging and ultrasensitive quantification of proteases in cancer cells by taking advantage of the characteristic luminescence and ICP-MS response of lanthanide metals. The nanoprobe is composed of a lanthanide metal-based luminescent donor/mass tag and a gold nanoparticle quencher linked by a specific peptide recognized by proteases. The protease activity in living cells is both visualized and quantified by monitoring the enzymatically released lanthanide metal using fluorescence imaging and ICP-MS. The low ppb level sensitivity of this method demonstrates its potential in the study of protease-dependent pathways and related diseases.